Process for preparing chiral dipeptidyl peptidase-IV inhibitors

摘要

A process for the preparation of pyrazolopyrolidines of structural formula I:;
and W is
;
or P, wherein in P is an amine protecting group. These compounds are useful in the synthesis of dipeptidyl peptidase-IV inhibitors for the treatment of Type 2 diabetes. Also provided are useful intermediates obtained from the process.

主权项

1. The process of preparing a compound of structural formula IIa: wherein Ar is phenyl optionally substituted with one to five R1 substituents; each R1 is independently selected from the group consisting of:
fluorine,chlorine,C1-6 alkyl, optionally substituted with one to five fluorines, andC1-6 alkoxy, optionally substituted with one to five fluorines; and R2 is selected from the group consisting of:
C1-6 alkyl; andC3-6 cycloalkyl; comprising the steps of:
forming a salt of formula I wherein W is H; and
forming a compound of formula II wherein P is an amine protecting group; Ar is phenyl optionally substituted with one to five R1 substituents; each R1 is independently selected from the group consisting of:
fluorine,chlorine,C1-6 alkyl, optionally substituted with one to five fluorines, andC1-6 alkoxy, optionally substituted with one to five fluorines; and R2 is selected from the group consisting of:
C1-6 alkyl; andC3-6 cycloalkyl, through reductive amination of the salt of formula I and a ketone of formula IV wherein P is an amine protecting group; Ar is phenyl optionally substituted with one to five R1 substituents; each R1 is independently selected from the group consisting of:
fluorine,chlorine,C1-6 alkyl, optionally substituted with one to five fluorines, andC1-6 alkoxy, optionally substituted with one to five fluorines; and R2 is selected from the group consisting of:
C1-6 alkyl; andC3-6 cycloalkyl.